NLRP1和NLRP3炎症小体及下游基因遗传多态与食管癌易感性及其功能学研究

项目名称： NLRP1和NLRP3炎症小体及下游基因遗传多态与食管癌易感性及其功能学研究

项目编号： No.81472332

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 顾海勇

作者单位： 江苏大学

项目金额： 55万元

中文摘要： 食管癌(Esophageal cancer, EC)在中国人群中的肿瘤死亡原因中排第4位，在常见肿瘤的诊断中排第5位。NLRP1和NLRP3炎症小体能促进白介素1β, 白介素18等炎症因子成熟，在EC发病过程中起重要作用。我们前期研究发现炎症小体下游基因白介素1β多态性和EC易感性存在显著关联。然而，上述关联不能全面的描述炎症小体相关基因多态性在EC易感性中的影响，研究只是对炎症小体个别相关基因进行初步的研究和分析，本研究采用大样本量，以医院为基础的两阶段病例对照研究，选择NLRP1和NLRP3炎症小体及其下游基因标签位点，深入探讨①NLRP1和NLRP3炎症小体及其下游基因的遗传多态单独或联合与中国人群EC易感性的关联；②NLRP1和NLRP3炎症小体及其下游基因的基因-基因，基因-环境交互作用；③功能性多态性位点的生物学功能。对EC的早期诊断、早期治疗等，研究结果具有重要意义。

中文关键词： C06_食管肿瘤；单核苷酸多态性；炎症小体

英文摘要： Esophageal cancer (EC) is of top fourth leading cause of cancer deaths and the fifth most common diagnosed cancer in China in 2009. NLRP1 and NLRP3 inflammasome may lead to the production of the active forms of interleukin 1β (IL-1β) and IL-18, which might contribute to cancer etiology. Single nucleotide polymorphisms (SNPs) may be important for EC susceptibility. Our recent studies have found some of inflammasome downstream IL-1β SNPs were significantly associated with EC susceptibility. The aim of our study is to thoroughly investigate inflammasome associated SNPs and EC risk. We use HapMap and high throughput genotype testing technology (SNPseq) and advanced molecular biology methods, conduct a hospital based two-stage case-control study, to investigate: (1) The association between inflammasome related SNPs and EC susceptibility; (2) Gene-gene and gene-environment (smoking, drinking, etc.) interactions; (3) The biological function of SNPs related with EC risk. We can obtain benefit from the results for early diagnosis and treatment of EC.

英文关键词： Esophageal cancer;SNP;inflammasomes